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AssigneeImmunoGen, Inc.
InventorsRavi Vankeepuram Jagannatha Chari, Wayne Charles Widdison
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The present invention provides a process for the preparation and purification of thiol-containing maytansinoids comprising the steps of: (1) reductive hydrolysis of a maytansinoid C-3 ester with a reducing agent selected from the group consisting lithium trimethoxyaluminum hydride (LiAl (OMe)3H), lithium triethoxyaluminum hydride (LiAl(OEt)3H), lithium tripropoxyaluminum hydride (LiAl (OPr)3H), sodium trimethoxyaluminum hydride (NaAl (OMe)3H), sodium triethoxyaluminum hydride (NaAl(OEt)3H) and sodium tripropoxyaluminum hydride (NaAl(OPr)3H) to yield a maytansinol; (2) purifying the maytansinol to remove side products when present; (3) esterifying the purified maytansinol with a carboxylic acid to yield a mixture of an L- and a D-aminoacyl ester of maytansinol; (4) separating the L-aminoacyl ester of maytansinol from the reaction mixture in (3); (5) reducing the L-aminoacyl ester of maytansinol to yield a thiol-containing maytansinoid; and (5) purifying the thiol-containing maytansinoid.
A process for preparing a thiol-containing maytansinoid wherein the thiol group is part of the ester moiety at C-3, comprising the steps of:
A process for isolating maytansinol from a mixture containing unreduced and over-reduced maytansinoids by separating the maytansinol by normal-phase high performance liquid chromatography (HPLC) on a chemically modified silica stationary phase.
A process for isolating maytansinol from a mixture containing unreduced and over-reduced maytansinoids by separating the maytansinol by large-scale preparative normal-phase high performance liquid chromatography (HPLC) on a chemically modified silica stationary phase.
Dependencies are inferred from the claim text.